Recombinant DNA technology can potentially make large quantities of specific gene sequences available for analysis. However, this technology is limited by the availability of specific nucleic acid probes for the detection and isolation of gene sequences. This grant proposes to establish a technology, based on synthetic oligonucleotide probes, for the screening of recombinant DNA libraries for specific gene sequences. The specific goals of this proposal are: 1. The characterization of the plaque screening technique using a bacteriophage lambda containing the rabbit beta-globin gene sequence and a chemically synthesized oligodeoxyribonucleotide probe complementary to the beta-globin mRNA. In addition, the hybridization of an oligonucleotide probe which is a mixture of all possible codon combinations for a particular region of the globin protein will be studied, such that only the correct sequence will hybridize in the plaque screening technique. 2. The molecular cloning of chromosomal DNA fragments from b-haplotype mice in the EK2 lambda-vector Charon 4A. 3. The isolation and analysis of the gene sequence for the major histocompability antigen, H-2Kb, from the library of cloned mouse DNA fragments using the mixed oligonucleotide screening approach established in (1) above.